FOCUS Small Research Project Title | Elucidating the Role of NOTCH1 in Impaired Cardiogenesis in Hypoplastic Left Heart Syndrome Using Vascularized Cardiac Tissue Derived from Human Pluripotent Stem Cells
Francisco Altamirano, phd
Department of Cardiovascular Sciences
Houston Methodist Research Institute & the Weill Cornell Medical College
Dr. Altamirano received his Ph.D. degree in Biomedical Sciences from the University of Chile. He has extensive experience studying the molecular mechanisms that drive striated muscle pathology. In 2015, Dr. Altamirano decided to join UT Southwestern for his postdoctoral training to study the role of Polycystin-1 in cardiovascular disease. His research focused on understanding how mutations in the gene PKD1 affect cardiac function. PKD1 encodes for Polycystin-1, a protein mutated in autosomal dominant polycystic kidney disease (ADPKD). Dr. Altamirano made the unexpected discovery that polycystin-1 (PC1) governs multiple voltage-gated potassium channels in cardiomyocytes, thereby affecting membrane repolarization and shaping cardiomyocyte action potential and cardiac function. Recently, Dr. Altamirano received a Career Development Award from the American Heart Association to continue his independent research. In 2020, as a new assistant professor, he started his lab at Houston Methodist Research Institute in Houston, aiming to uncover the role of Polycystin-1 in cardiovascular function and electrical remodeling.
Francisco alvarado, pharmd, phd
Dept. of Medicine, Cardiovascular Research Center
University of Wisconsin-Madison
Dr. Alvarado trained as a Pharmacist at the University of Costa Rica and moved to the United States in 2011 to attend graduate school. He received a PhD in Molecular and Integrative Physiology from the University of Michigan and joined the Cardiovascular Research Center at the University of Wisconsin- Madison. His main research interest is on the role of calcium as a critical second messenger and how dysregulation of calcium homeostasis may lead to heart disease. His favorite protein is the cardiac ryanodine receptor (RyR2), the major calcium release channel in the heart. During his graduate/postdoctoral training, he developed a strong background in cardiac electrophysiology and calcium handling in the normal and diseased hearts, while characterizing a novel RyR2 mutation from a patient with hypertrophic cardiomyopathy. His current research focuses on novel mechanisms of cardiac arrhythmia in a rabbit model of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited syndrome caused mainly by mutations in RyR2. He has experience in a wide range of techniques, including the measurement of cellular calcium signals with confocal microscopy, pharmacological studies with radioligands, patch clamp, Langendorff perfusion of isolated hearts, and in vivo recordings of electrocardiograms and intracardiac electrical activity. As a junior investigator in the process of establishing his research niche, he is looking to establish new collaborations, learn new experimental approaches and expand the scope of his work. Hence, he is thrilled to participate in FOCUS.
Irene Cal Y Mayor Turnbull, Md
Cardiovascular Research Center
Icahn School of Medicine at Mount Sinai
Dr. Cal y Mayor Turnbull's work involves fabricating human engineered cardiac tissues (hECT) from human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes, and their application as in vitro platforms to test the efficacy and possible cardio toxicity of novel therapies, including both gene and cell therapy approaches. Her work in tissue engineering technologies has involved three main areas of research, 1) the investigation of cell-based therapy approaches for improving cardiac contractility, 2) the development of 3D human myocardium models of acquired cardiomyopathies, and 3) the development of 3D human myocardium models of inherited cardiomyopathies using gene editing and gene therapy approaches combined with human iPSC technology. For her future research project, she aims to investigate the mechanisms through which non-cardiomyocytes can impact cardiomyocyte function. She will be fabricating hECT with hiPSC derived cardiomyocytes, and she will also fabricate heterotypic tissues, where, in addition to the cardiomyocyte component, she will include non-cardiomyocyte cells, using hiPSC derived -fibroblasts, -smooth muscle and -endothelial cells. After functional and structural characterization, she plans to perform RNA seq to identify the molecular signature differences between hCM-only vs. heterotypic hECT.
Dr. DeLeon-Pennell's research background is in dissecting the interplay of pre-existing variables, such as chronic inflammation or sex, on cardiovascular events. These changes include cell-matrix interactions, which both affect and react to processes involved in tissue repair. The immediate goal of her research is to determine how cross-talk between the innate and adaptive immune system regulates the fibrotic process ultimately leading to adverse remodeling following myocardial infarction (MI). She is the first person to demonstrate that the co-existing chronic inflammation due to a periodontal pathogen leads to adverse LV remodeling and thus facilitating in poor prognosis post-MI. It was her research in this area that gave rise to the idea that CD8+ T-cell activation may be a negative regulator of post-MI remodeling by regulating the innate immune system. In 2017, she was awarded a career development award from the VA on first submission to pursue her research interests on the effects of CD8+ T-cells on cardiac remodeling post-MI. In 2018, she moved and started her lab at the Medical University of South Carolina and the Ralph H Johnson VA Medical Center. For her R01/VA Merit submission, she would like to expand on this project and evaluate the role of CD8+ T-cells on macrophage physiology. For this project, she hypothesizes that CD8+ T-cells regulate the cardiovascular wound healing process by activating, killing, and removing monocyte-derived macrophages from the infarct.
Demetria mcneal, phd, mba
Dept. of Medicine, Div. of General Internal Medicine
University of Colorado, Anschutz Medical Campus
Dr. McNeal is an academically trained health communication scientist with pharmaceutical industry, healthcare consulting and clinical experience. Her unique skill set as an academic researcher with realworld healthcare management and consultant experience positions her to advance the fields of health equity research and dissemination and implementation science through novel approaches to improve patient outcomes and health care delivery. Dr. McNeal previously completed two postdoctoral fellowships, in the University of Colorado Adult and Child Consortium for Health Outcomes Research and Delivery Science (ACCORDS) Center and with the Veterans Health Administration (VA) in Health Services Research and Delivery Science. Her overarching research goal is to reduce health inequities in cardiovascular disease treatment and healthcare delivery, particularly in the African American population. To achieve this overarching goal, Dr. McNeal seeks to work in partnership with health care systems, clinics and local communities to implement and disseminate evidence-based programs to improve cardiovascular outcomes in African Americans.
Sam Senyo, PHD
Department of Biomedical Engineering
Case Western Reserve University
Dr. Senyo joined CWRU-BME in 2016 after a postdoctoral fellowship cardiac regenerative biology at Brigham & Women’s Hospital. His early work examined the source of slow turnover in the mammalian heart using stable isotope imaging. His laboratory continues to investigate cardiac regeneration with a focus on mechano-biology and extracellular stimuli. His research program aims to reverse effects of disease and aging that impair regeneration potential with the efforts of a multidisciplinary team. His trainees come from around the world: Asia, Africa, Europe, US, and Caribbean. As a team, his lab employs microfluidics, molecular biology, and tissue engineering as our primary tools, and he has purposely selected students with a diverse background across engineering disciplines and material science. Since his faculty appointment, he has been lead-lecturer of four courses. He has recently narrowed his classes to a Tissue Engineering course and a Biomaterials course. The classes complement research topics in his lab and allow him to devote a majority of his attention to his research. The pandemic levels of diabetes and obesity in the US have extended the lab focus to include diabetic cardiomyopathy that overlaps with aspects of other forms of cardiovascular disease. Ultimately, his fascination with novel biological paradigms approached from an engineering perspective has driven a lot of his work to date.
Dr. Sweeney is board certified in general pediatrics and pediatric cardiology. She earned her undergraduate degree from Springfield College, Springfield, MA and her graduate degrees from the University of Texas at El Paso, TX and the Johns Hopkins University- Bloomberg School of Public Health in Baltimore, MD. She obtained her medical degree from Columbia University College of Physicians and Surgeons, NY, NY and completed a pediatric residency at Johns Hopkins Hospital in Baltimore, MD. Dr. Sweeney completed her pediatric cardiology fellowship at Lucile Packard Children’s Hospital-Stanford University, CA. After completion of her cardiology fellowship, she remained at Stanford as a clinician in the cardiovascular intensive care unit (CVICU) and an academic staff researcher investigating potential pathways and modifier genes leading to familial tetralogy of Fallot (TOF) by enrolling families with multiple members affected with various phenotypes of TOF in a Whole Exome Sequencing (WES) study. She has experience in both translational and basic science research. She subsequently moved to University of California San Diego to complete a Neonatal-Perinatal Medicine Fellowship in an effort to better care for the neonate with congenital heart disease (CHD). Dr. Sweeney is interested in the application of individualized medicine in the care of neonates with suspected genetic disease, especially those with CHD. Her research at Rady Children's Institute for Genomic Medicine focuses on identifying genotypic differences via rapid genomic sequencing that may explain the observed phenotypes with the goal of offering prompt, directed, accurate, personalized care to patients in the intensive care unit and beyond.